title: Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis.
abstract: Phosphatidylinositol 3-kinase α (PI3Kα) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3Kα can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3- and 6-positions of imidazo[1,2-a]pyridines, we studied the structure-activity relationships (SAR) profiles and identified a series of potent PI3Kα inhibitors. Representative derivatives showed good activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.
authors.affiliation: Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Okseon
authors.initials: O
authors.lastname: Kim
authors.forename: Yujeong
authors.initials: Y
authors.lastname: Jeong
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.forename: Sun-Sun
authors.initials: SS
authors.lastname: Hong
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Hong
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011487:Protein Conformation; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines